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Objectives: To investigate the clinical and molecular epidemiological characteristics of blaIMP-4-carrying Klebsiella pneumoniae in a tertiary hospital in China. Methods: Ten carbapenem-resistant K. pneumoniae (CRKP) isolates carrying the blaIMP-4 gene were collected. Molecular characteristics were analysed using whole-genome sequencing. Plasmid conjugation experiments were used to analyse conjugation of the plasmids. We compared and analysed K. pneumoniae-carrying blaIMP-4 genomic datasets obtained from the National Center for Biotechnology Information (NCBI) with the strains in this study. Results: All 10 CRKP isolates carrying blaIMP-4 were collected from 10 adult patients in the respiratory intensive care unit. These strains were only sensitive to polymyxins and tigecycline due to them simultaneously carrying multiple resistance genes, namely blaOKP-A-5, fosA, oqxA, and oqxB. Notably, R29 harboured two carbapenemase genes (blaNDM-1 and blaIMP-4). These strains had similar drug-resistant phenotypes and genes, all belonging to sequence type (ST)196. Additionally, the patients had experienced spatiotemporal intersection during hospitalization, suggesting that these strains underwent clonal transmission, but they belonged to different clonal clusters from the blaIMP-4-positive K. pneumoniae currently published in the NCBI. Among the 10 strains, blaIMP-4 was located on the IncN plasmid, and six strains had successfully transferred the plasmid to the recipient strain EC600 through plasmid conjugation. Conclusions: The blaIMP-4-positive ST196 CRKP isolate showed clonal distribution in the respiratory intensive care unit, which was mediated by the IncN plasmid. Consequently, there should be increased monitoring of carbapenem-resistant strains in clinical settings to prevent and control its transmission.

Summary: Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC210) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC210 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC210 conferred superior protection from GVHD than IL-10−/low ILC2s, and blocking IL-10 and IL-4 abrogated ILC210 protective effects, indicating that these cytokines are important for the protective effects of ILC210. Notably, ILC210 provided comparable protection from GVHD to regulatory T cells without impairing T cell engraftment, instead decreasing intestinal T cell infiltration and suppressing CD4+ Th1 and CD8+ Tc1 cells. CITE-seq of expanded ILC2s revealed CD49d and CD86 are markers that allow for enrichment of ILC210 from conventional ILC2s and tracking of ILC210 in patient studies. Altogether, these findings demonstrate the potential of ILC210 in cell therapies for GVHD and other immune-mediated diseases.

Abstract Background Shewanella xiamenensis, widely distributed in natural environments, has long been considered as opportunistic pathogen. Recently, significant changes in the resistance spectrum have been observed in S. xiamenensis, due to acquired antibiotic resistance genes. Therefore, a pan-genome analysis was conducted to illuminate the genomic changes in S. xiamenensis. Results Phylogenetic analysis revealed three major clusters and three singletons, among which close relationship between several strains was discovered, regardless of their host and niches. The “open” genomes with diversity of accessory and strain-specific genomes took advantage towards diversity environments. The purifying selection pressure was the main force on genome evolution, especially in conservative genes. Only 53 gene families were under positive selection pressure. Phenotypic resistance analysis revealed 21 strains were classified as multi-drug resistance (MDR). Ten types of antibiotic resistance genes and two heavy metal resistance operons were discovered in S. xiamenensis. Mobile genetic elements and horizontal gene transfer increased genome diversity and were closely related to MDR strains. S. xiamenensis carried a variety of virulence genes and macromolecular secretion systems, indicating their important roles in pathogenicity and adaptability. Type IV secretion system was discovered in 15 genomes with various sequence structures, indicating it was originated from different donors through horizontal gene transfer. Conclusions This study provided with a detailed insight into the changes in the pan-genome of S. xiamenensis, highlighting its capability to acquire new mobile genetic elements and resistance genes for its adaptation to environment and pathogenicity to human and animals.

Abstract Background Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. Methods Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. Results A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including bla GES−1 (10/47), bla VIM−2 (6/47), bla GES−14 (4/47), bla IMP−45 (2/47), bla KPC−2 (1/47), and bla NDM−14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4–O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018–2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried bla GES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). Conclusions The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying bla GES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.

Corrosion of soft magnetic materials during service can significantly impact their performance and service life, therefore it is important to improve their corrosion resistance. In this paper, the corrosion resistance, alternating current soft magnetic properties (AC SMPs) and microstructure of FeCoNixAl (x = 1.0–2.0) medium-entropy alloys (MEAs) were studied. Corrosion resistance is greatly improved with an increase in Ni content. The x = 2.0 alloy has the lowest corrosion current density (Icorr = 2.67 × 10−7 A/cm2), which is reduced by 71% compared to the x = 1.0 alloy. Increasing the Ni content can improve the AC SMPs of the alloy. When x = 1.75, the total loss (Ps) is improved by 6% compared to the x = 1.0 alloy. X-ray diffraction (XRD) and scanning electron microscopy (SEM) show that the increase in Ni content is beneficial for promoting the formation of the face-centered-cubic (FCC) phase, and the body-centered-cubic (BCC) phase is gradually divided by the FCC phase. Electron backscatter diffraction (EBSD) shows that, with the increase in Ni content, the number of grain boundaries in the alloy is greatly reduced and numerous phase boundaries appear in the alloys. The degree of strain concentration is significantly reduced with the increasing Ni content. The corrosion mechanism of alloys is also discussed in this paper. Our study provides a method to balance the soft magnetic properties and corrosion resistance, paving the way for potential applications of Fe-Co-Ni-Al MEAs in corrosive environments.

ObjectivePrevious observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level.MethodsA two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (P

Abstract Non-small cell lung cancer (NSCLC) is the malignant tumor with the highest morbidity and leading cause of death worldwide, whereas its pathogenesis has not been fully elucidated. Although mutations in some crucial genes in WNT pathways such as β-catenin and APC are not common in NSCLC, the abnormal signal transduction of WNT pathways is still closely related to the occurrence and progression of NSCLC. WNT ligands (WNTs) are a class of secreted glycoproteins that activate WNT pathways through binding to their receptors and play important regulatory roles in embryonic development, cell differentiation, and tissue regeneration. Therefore, the abnormal expression or dysfunction of WNTs undoubtedly affects WNT pathways and thus participates in the pathogenesis of diseases. There are 19 members of human WNTs, WNT1, WNT2, WNT2b, WNT3, WNT3a, WNT4, WNT5a, WNT5b, WNT6, WNT7a, WNT7b, WNT8a, WNT8b, WNT9a, WNT9b, WNT10a, WNT10b, WNT11 and WNT16. The expression levels of WNTs, binding receptors, and activated WNT pathways are diverse in different tissue types, which endows the complexity of WNT pathways and multifarious biological effects. Although abundant studies have reported the role of WNTs in the pathogenesis of NSCLC, it still needs further study as therapeutic targets for lung cancer. This review will systematically summarize current research on human WNTs in NSCLC, from molecular pathogenesis to potential clinical practice.

Primary liver cancer is characterized by closely related with chronic liver inflammation, thereby reversing hypoxic immunosuppressive microenvironment of tumor cell growth by immunotherapy drug is a potentially effective strategy. Camrelizumab is an anti-PD-1 antibody being developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd. We reported a case of an adult critical Chinese patient with primary hepatocellular carcinoma and lung metastasis completely responding to Camrelizumab, most of the lesions were stable and no new lesions occurred after 1-year treatment, which provides us to reconsider the therapeutic effect of Camrelizumab on such patients. Camrelizumab had a safety profile for the patient in our case report, except for the occurrence of RCCEP. This case provides the evidence of the effective antitumor activity and manageable toxicities of Camrelizumab for patients with advanced hepatocellular carcinoma, which was the first application as far as we know.

Clear cell renal cell carcinoma (ccRCC) is the most common histological type of renal carcinoma and has a high recurrence rate and poor outcome. Accurate patient risk stratification based on genetic markers can help to identify the high-risk patient for early and further treatments and would promote patient survival. Long non-coding RNAs (lncRNAs) have attracted widespread attention as biomarkers for early diagnosis, treatment, and prognosis because of their high specificity and sensitivity. Here, we performed a systematic search in NCBI PubMed and found 44 lncRNAs as oncogenes, 18 lncRNAs as tumor suppressors, 199 lncRNAs as diagnostic biomarkers, 62 lncRNAs as prognostic biomarkers, and 3 lncRNAs as predictive biomarkers for ccRCC. We also comprehensively discuss the biological functions and molecular regulatory mechanisms of lncRNAs in ccRCC. Overall, the present study is a systemic analysis to assess the expression and clinical value of lncRNAs in ccRCC, and lncRNAs hold promise to be diagnostic, prognostic, and predictive biomarkers.

The data element-driven industry (DEDI) generates large amounts of data, thereby mitigating information asymmetry. Does this affect corporate cash holdings? On the basis of theoretical analysis, this study empirically analyzes the impact of DEDI on enterprises' cash holdings and its transmission path using data of Chinese cities and A-share listed enterprises from 2008 to 2020. First, the results indicate that the DEDI reduces corporate cash holdings. As the development level of the DEDI improves, the corporate cash holdings gradually decrease. Second, the DEDI indirectly affects corporate cash holdings by influencing debt-financing and external credit supply capacities. Specifically, the DEDI increases the upstream corporate debt-financing and downstream corporate external credit supply capacities. Improvements in debt-financing and the external credit supply capacities can reduce corporate cash holdings. Third, the DEDI has a heterogeneous impact. For enterprise with CEO duality, small and medium-sized, and information technology enterprises, the impact of DEDI in reducing cash holdings is greater.

Long noncoding RNAs (lncRNAs) have been implicated in various biological processes and pathological conditions, including tumorigenesis. However, the exact roles of NEAT1 and its underlying mechanisms in nonsmall cell lung cancer (NSCLC) remain largely unclear. In the present study, lncRNA NEAT1 was detected to be significantly upregulated in NSCLC tissues and closely associated with advanced TNM stages, lymph node metastasis, distant metastasis, and poor prognosis. Further experiments revealed that lncRNA NEAT1 silencing inhibited cell proliferation and invasion in vitro. In addition, mechanistic analysis showed that lncRNA NEAT1 upregulated the miR-181a-5p-targeted gene HMGB2 through acting as a competitive "sponge" of miR-181- a-5p. In conclusion, our study suggested that lncRNA NEAT1 plays an oncogenic role in NSCLC progression and provides potential mechanisms by which lncRNA NEAT1 contributes to this disease. [ABSTRACT FROM AUTHOR]